OVERALL PROJECT SUMMARY/ABSTRACT! Now in its 43rd year as an NCI-Designated Comprehensive Cancer Center, Yale Cancer Center (YCC) has established a strong tradition of high-impact cancer research and a deep culture of communication and collaboration that unites 286 basic, translational, population, and clinical scientists representing all biomedical disciplines. YCC arms these investigators with a suite of enabling cores and powerful collaborative opportunities and resources. Through intra- and inter-programmatic collaboration, the overarching goals of YCC are to understand and prevent cancer, detect cancer early, and manage cancer treatment more accurately and effectively. The seven Research Programs are the heart of YCC, and each program is led by a basic scientist in partnership with a clinical/translational scientist to foster transdisciplinary research and the advancement of Yale science from the bench to the clinic. In addition, YCC supports and manages Shared Resources that provide unique expertise and enabling technologies that enrich the scope and expedite progress of each Research Program. YCC infrastructure further enables ground-breaking clinical trials that capitalize on Yale science and incorporate novel designs and biomarker assessments to optimize patient selection, define treatment resistance, and inform new therapeutic approaches. Overall cancer funding (direct costs) has increased 51% from $58.2M in 2012 to $88M in 2017, including an increase from $17.8M to $23.5M in NCI funding (direct costs). YCC holds two NCI SPORE grants, a UM1, U10, multiple P01s, numerous multi- investigator R01 grants, and leadership in two SU2C Dream Team awards. Additionally, during the current funding cycle, YCC leveraged $5.9M, reflecting CCSG Developmental Funds and institutional support, to advance new research and collaborations, resulting in $55.6M in new extramural funding - a 9-fold return on investment. During the same period, accrual to interventional treatment trials increased 82%, from 471 to 859, and accruals to early-phase treatment trials (pilot, I, I-II) increased three-fold, now representing 44% of total treatment accruals. No less important, YCC has expanded and invested in initiatives and research that seeks to impact cancer inequities and the needs of our catchment area at an individual, institutional, and policy level. Over the next five years, YCC will continue to develop initiatives and resources to foster innovation, collaboration, excellence and synergy to maximize the impact of Yale?s talent and expertise on the understanding, prevention and treatment of cancer.!